Dopamine acts upon neurons through two families of dopamine receptors, D1-like receptors (D1Rs) and D2-like receptors (D2Rs). The D1-like receptor family consists of D1 and D5 receptors which are expressed in many regions of the brain. D1 mRNA has been found, for example, in the striatum and nucleus accumbens. See e.g., Missale C, Nash S R, Robinson S W, Jaber M, Caron M G “Dopamine receptors: from structure to function”, Physiological Reviews 78:189-225 (1998). Pharmacological studies have reported that D1 and D5 receptors (D1/D5), namely D1-like receptors, are linked to stimulation of adenylyl cyclase, whereas D2, D3, and D4 receptors, namely D2-like receptors, are linked to inhibition of cAMP production.
Dopamine D1 receptors are implicated in numerous neuropharmacological and neurobiological functions. For example, D1 receptors are involved in different types of memory function and synaptic plasticity. See e.g., Goldman-Rakic P S et al., “Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction”, Psychopharmacology 174(1):3-16 (2004). Moreover, D1 receptors have been implicated in a variety of psychiatric, neurological, neurodevelopmental, neurodegenerative, mood, motivational, metabolic, cardiovascular, renal, ophthalmic, endocrine, and/or other disorders described herein including schizophrenia (e.g., cognitive and negative symptoms in schizophrenia), schizotypal personality disorder, cognitive impairment associated with D2 antagonist therapy, ADHD, impulsivity, autism spectrum disorder, mild cognitive impairment (MCI), age-related cognitive decline, Alzheimer's dementia, Parkinson's disease (PD), Huntington's chorea, depression, anxiety, treatment-resistant depression (TRD), bipolar disorder, chronic apathy, anhedonia, chronic fatigue, post-traumatic stress disorder, seasonal affective disorder, social anxiety disorder, post-partum depression, serotonin syndrome, substance abuse and drug dependence, Tourette's syndrome, tardive dyskinesia, drowsiness, sexual dysfunction, migraine, systemic lupus erythematosus (SLE), hyperglycemia, dislipidemia, obesity, diabetes, sepsis, post-ischemic tubular necrosis, renal failure, resistant edema, narcolepsy, hypertension, congestive heart failure, postoperative ocular hypotonia, sleep disorders, pain, and other disorders in a mammal. See e.g., Goulet M, Madras B K “D(1) dopamine receptor agonists are more effective in alleviating advanced than mild parkinsonism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys”, Journal of Pharmacology and Experimental Therapy 292(2):714-24 (2000); Surmeier D J et al., “The role of dopamine in modulating the structure and function of striatal circuits”, Prog. Brain Res. 183:149-67 (2010).
New or improved agents that modulate (such as agonize or partially agonize) D1R are needed for developing new and more effective pharmaceuticals to treat diseases or conditions associated with dysregulated activation of D1R, such as those described herein.
WO2013026516 reports bicyclic heteroaromatic compounds having the following structure
that are kinase inhibitors and can be used, for example, for treating tumors.
CN102558147 reports pyridinecarboxamide derivatives of the following formula:
as inhibitors of tyrosine kinase and/or serine-threonine kinase for treating cancer.
WO2007009524 reports 2-arylbenzothiazoles of the following formula
useful as protein kinase inhibitors for treating diseases such as those associated with abnormal and hyperproliferation of cells.
US2005/0153989 reports compounds of the following structure
useful for treating and/or preventing conditions and diseases associated with kinase activity, e.g., EGFR activity, such as cancer, hyperplasia, psoriasis, cardiac hypertrophy, arthrosclerosis, dermatitis and/or diseases or conditions associated with undesired cellular hyperproliferation.
Abou-Zeid, K. A. M. et al, “synthesis of 6-(4-(substituted amino)phenyl)-4,5-dihydropyridazin-3(2H)-ones as potential positive inotropic agents,” Egyptian Journal of Pharmaceutical Sciences (1998), Volume Date 1997, 38(4-6), 319-331, reports some pyridazinones, for example,
that were evaluated as inhibitors of cardiac cAMP phosphodiesterase.
Demange, L. et. al, “Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer's disease,” Medicinal Chemistry Research (2013), 22(7), 3247-3258 reports compounds having one of following structures
as inhibitors of CK1 and CDK5. In addition, it also reports certain intermediates having one of the following structures:

US20100317646 reports pyrazolopyridine compounds of the following structure
as kinase inhibitors (e.g., LRRK or LRRK2 inhibitors).
US20100247517 reports compounds having one of the following structures
useful for the production of pharmaceutical compositions for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.
Bischoff, F. et. al, “Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators,” Journal of Medicinal Chemistry (2012), 55(21), 9089-9106 reports certain imidazole containing compounds γ-secretase modulators including the following two compounds:

US2012/0022090 reports substituted benzoxazole, benzimidazole, oxazolopyridine, and imidazopyridine derivative of the following structure
that are γ-secretase modulators useful in the treatment of diseases.
US2011/0281881 reports substituted bicyclic derivative of the following structure
wherein Het2 can be
as γ-secretase modulators useful in the treatment of diseases such as Alzheimer's Disease.WO2008067420 reports compounds of one of the flowing structures
or pharmaceutically acceptable salts, proudrugs, or tautomers thererof, as caspase activators and inducers of apoptosis.